Microfluidics apparatus and methods of use therefor

ABSTRACT

A microfluidics device includes a plurality of interaction cells and fluid control means including i) means for providing to the interaction cells a preparation fluid, and ii) means for providing to the interaction cells a sample fluid, wherein each interaction cell receives a different sample fluid. A plurality of microcantilevers may be disposed in each of the interaction cells, wherein each of the plurality of microcantilevers configured to deflect in response to an interaction involving a component of the sample fluid.

The present application is a continuation-in-part of the applicationentitled “Microfluidics Apparatus and Methods of Use Therefor” Ser. No.______ bearing Attorney Docket 2506/129 which was filed in the UnitedStates Patent and Trademark Office on Nov. 9, 2001, and which isincorporated herein by reference.

TECHNICAL FIELD

The present invention relates to chemical analysis, and in particular tomethods and apparatuses for performing chemical analysis of biomaterialswith a microfluidics device using microcantilevers.

BACKGROUND OF THE INVENTION

It is known that thin bimorph microcantilevers can undergo bending(deflection) due to differential stresses following exposure to andbinding of a compound from their environment, for example in a fluidsample. Soft microcantilevers having spring constants less than 0.1 N/mare sensitive to stress differentials that arise as a result ofinteractions between extremely small amounts of a substrate material ona surface of the microcantilever and one or more materials in a sample.For a given microcantilever with a specially designed coating layer, thedeflection yields information about components of the environment towhich the microcantilever is exposed.

Microcantilevers are capable of detecting calorimetric enzyme-mediatedcatalytic biological reactions with femtojoule resolution. (Thundat etal., “Microcantilever Sensors”, Microscale Thermophysical Engr. 1, pgs.185-199, 1997.) Further, oligonucleotide interactions within a samplecan be detected using a monolithic array of test sites formed on asurface to which the sample is applied as shown in U.S. Pat. No.5,653,939.

It is also known to provide integrated chips to categorize molecules ina biochemical sample. For example, U.S. Pat. No. 6,123,819 to Peetersdiscloses a design for an integrated chip having an array of electrodesat the atomic or nano scale. The chip can be used to characterize singlemolecules in a solution such as individual proteins, complex proteinmixtures, DNA, or other molecules.

In recent years, microfludics technology employing microcantilevers hasemerged to provide a “lab-on-a-chip” for chemical analysis ofbiomaterials. For example, U.S. Pat. No. 6,054,277 to Furcht et al.discloses a genetic testing system that includes an integrated, unitarymicrochip-based detection device with microfluidic controls. The deviceemploys a microcantilever sensor to detect a biochemical reaction in asingle detection chamber having capillary interconnects. However, toanalyze a number of solutions simultaneously, it would be necessary toutilize an equal number of these chips.

SUMMARY OF THE INVENTION

In one embodiment, a microfluidics device is provided. The microfluidicsdevice comprises a plurality of interaction cells and fluid controlmeans, including: i) means for providing to the interaction cells apreparation fluid, and ii) means for providing to the interaction cellsa sample fluid, wherein each interaction cell receives a differentsample fluid. In a related embodiment, a plurality of microcantileversis disposed in each of the interaction cells, each of the plurality ofmicrocantilevers being configured to deflect in response to aninteraction involving a component of the sample fluid. The fluid controlmeans may include means for removing a fluid from the interaction cells.The fluid control means may be robotic or it may be manual.Additionally, the plurality of microcantilevers may be provided as aplurality of fingers in a planar array. In accordance with anotherrelated embodiment, the microfluidics device is disposable. In anotherrelated embodiment, the microfluidics device is reusable.

In accordance with another embodiment, a microcantilever platformincludes a plurality of interaction cells, each of the interaction cellsincluding an inlet for receiving a sample fluid, wherein each of theinteraction cells receives a different sample fluid; at least onemicrocantilever is disposed in each of the interaction cells, themicrocantilever being capable of deflecting in response to chemicalinteraction with a component of the sample fluid. In relatedembodiments, each interaction cell further includes at least one outletwhereby fluid may flow out of the cell. The microcantilever platform maybe disposable or reusable.

In accordance with a further embodiment, an apparatus is provided forperforming microfluidics analysis, which apparatus includes a housingcomprising a plurality of fluid lines; each of the fluid lines includesan inlet for receiving a fluid from a fluid pump and a plurality ofcontrol lines in communication with the fluid lines, each of the controllines including an inlet for receiving a control fluid; the apparatusalso includes a microfluidics device having a plurality of interactioncells, each of the interaction cells including an inlet for receivingone or more preparation fluids and a sample fluid, and wherein each ofthe interaction cells receives a different sample fluid; each of theinteraction cells also includes an outlet whereby fluid may flow out ofthe interaction cell; each of the interaction cells may also include atleast one microcantilever configured to deflect in response to chemicalinteractions with a component of the sample fluid; and the apparatusfurther includes a plurality of valves in communication with the fluidlines for controlling the flow of fluid into and out of the interactioncells.

The apparatus may further include a plurality of microcantileversdisposed in each interaction cell, and the plurality of microcantileversmay be provided in a planar array having a plurality of fingers. Inaccordance with related embodiments, the control fluid is a gas. Thenumber of the plurality of valves may be less than the number of theplurality of fluid lines. Similarly, the number of the plurality ofvalves may be less than the number of the plurality of control lines. Inaccordance with further related embodiments, the apparatus is mounted ona temperature-controlled platform.

The apparatus may also include a plurality of expansion chambers foreliminating gas from fluid entering the interaction cells, and/or awaste receptacle for receiving fluid from the outlets of the interactioncells. In accordance with further related embodiments, the apparatus mayalso include a reservoir for sample collection from each outlet of eachinteraction cell, and the sample collected in at least one of thereservoirs may be subject to further analysis. The further analysis mayinclude gel electrophoresis, for example, the gel electrophoresis may bemulti dimensional. At least one of the dimensions may be polyacrylamidegel electrophoresis in the presence of a denaturing detergent. Thefurther analysis may also include mass spectroscopy.

In accordance with another embodiment, a method is provided foridentifying an analyte in a plurality of sample fluids. The methodincludes causing a preparation solution to flow into one or more of aplurality of interaction cells, wherein each of the interaction cellsincludes at least one microcantilever, and the preparation fluidincludes a ligand that binds to the microcantilever and has affinity forthe analyte; at least one sample solution flows into the one or moreinteraction cells, and a deflection of the microcantilever in eachinteraction cell having sample solution containing the analyte isdetected.

In accordance with related embodiments, causing the preparation solutionto flow into one or more of the plurality of interaction cells furtherincludes causing a linker solution to flow into one or more of theinteraction cells, wherein the linker solution is capable of binding theligand to the microcantilever. Causing the preparation solution to flowinto one or more of the plurality of interaction cells may furtherinclude causing a wash solution to flow into one or more of theinteraction cells. Additionally, causing a preparation solution to flowinto one or more of the plurality of interaction cells also includescausing a receptor solution to flow into one or more of the interactioncells and/or causing a buffer solution to flow into one or more of theinteraction cells. In accordance with related embodiments, the methodmay include mounting the interaction cells on a temperature-controlledplatform.

In accordance with further related embodiments, the number of samplesolutions may equal the number of interaction cells. Similarly thenumber of sample solutions may be less than the number of interactioncells. The ligand may be selected from a group consisting of a proteinand a nucleic acid, and the nucleic acid may be RNA or DNA. The proteinmay be may be an epitope, an enzyme, or a polypeptide, and the analytemay be selected from a group consisting of all or a portion of a nucleicacid and a protein. The analyte may also be a hormone, and the hormonemay be selected from a group consisting of a steroid and a polypeptide.In another related embodiment, the ligand and the analyte are eachselected from a group consisting of an antibody and an antigen.

In accordance with yet another embodiment of the invention,microfluidics device includes a housing comprising a plurality of fluidlines. Each of the fluid lines includes an inlet for receiving a fluidfrom a fluid pump disposed within the housing. The housing also includesa plurality of control lines in communication with the fluid lines,wherein each of the control lines includes an inlet for receiving acontrol fluid. The embodiment also includes a microcantilever platformhaving a plurality of interaction cells. Each of the interaction cellsincludes an inlet for receiving one or more preparation fluids and asample fluid and an outlet whereby fluid may flow out of the interactioncell. Additionally, each of the interaction cells receives a differentsample fluid. A plurality of valves is in communication with the fluidlines for controlling the flow of fluid into and out of the interactioncells.

BRIEF DESCRIPTION OF THE DRAWINGS

The foregoing features of the invention will be more readily understoodby reference to the following detailed description, taken with referenceto the accompanying drawings, in which:

FIG. 1 is a graphical illustration showing a bottom view of an apparatusfor performing microfluidic analysis in accordance with an embodiment ofthe invention;

FIG. 2 is a graphical illustration showing a top view of the apparatusof FIG. 1;

FIG. 3 is a graphical illustration of the embodiment of FIG. 1 showingall valves closed;

FIG. 4 is a graphical illustration of the embodiment of FIG. 1 showing alinker solution added to a first interaction cell;

FIG. 5 is a graphical illustration of the embodiment of FIG. 1 showing alinker solution added to a second interaction cell;

FIG. 6 is a graphical illustration of the embodiment of FIG. 1 showing alinker solution added to a third interaction cell;

FIG. 7 is a graphical illustration of the embodiment of FIG. 1 showing alinker solution added to a fourth interaction cell;

FIG. 8 is a graphical illustration of the embodiment of FIG. 1 showing awash solution added to a first interaction cell;

FIG. 9 is a graphical illustration of the embodiment of FIG. 1 showing aligand solution added to a first interaction cell;

FIG. 10 is a graphical illustration of the embodiment of FIG. 1 showinga buffer solution added to a first interaction cell;

FIG. 11 is a graphical illustration of the embodiment of FIG. 1 showinga sample solution added to a first interaction cell;

FIG. 12 is a graphical illustration of the embodiment of FIG. 1 showinga sample solution added to a second interaction cell;

FIG. 13 is a graphical illustration of the embodiment of FIG. 1 showinga sample solution added to a third interaction cell;

FIG. 14 is a graphical illustration of the embodiment of FIG. 1 showinga sample solution added to a fourth interaction cell;

FIG. 15 is a graphical illustration of an apparatus for performingmicrofluidic analysis in accordance with another embodiment of theinvention;

FIG. 16 is a graphical illustration of the embodiment of FIG. 15 showinga solution added to a first interaction cell;

FIG. 17 is a graphical illustration of the embodiment of FIG. 15 showinga solution added to a second interaction cell;

FIG. 18 is a graphical illustration of the embodiment of FIG. 15 showinga solution added to a third interaction cell;

FIG. 19 is a graphical illustration of the embodiment of FIG. 15 showinga solution added to a fourth interaction cell; and

FIG. 20 is a schematic flow chart illustrating a fluidics system for usein accordance with a method for identifying an analyte in a plurality ofsample fluids in accordance with a further embodiment of the invention.

DETAILED DESCRIPTION OF SPECIFIC EMBODIMENTS

FIG. 1 is a graphical illustration showing a bottom view of an apparatusfor performing microfluidic analysis in accordance with an embodiment ofthe invention. The apparatus includes three dimensional a housing 150having a plurality of fluid lines 141-148. The fluid lines 141-148 aredisposed within the housing in at least two layers such that some fluidlines are closer to a top face of the housing 155 and others are closerto a bottom face of the housing 156, shown in FIG. 2. Each of the fluidlines has an inlet 131-138 for receiving a fluid from a fluid pump orother fluid delivery apparatus. Such a fluid pump may be external to thehousing 150 or it may be part of the housing so as to create acompletely self-contained unit. The housing 150 also includes aplurality of control lines 111-120 in communication with valves 161-170.Valves 161-166 are in communication with the fluid lines 141-148. Eachof the control lines 111-120 receives a control fluid, such as a gas orother fluid, from an inlet 101-110. The fluid lines 141-148, controllines 111-120 and fluid paths (discussed below) may be about 0.5 mm indiameter. For example, the diameter of the lines and paths may rangefrom about 0.05 mm to about 0.6 mm. In accordance with furtherembodiments of the invention, the diameter of the lines and paths may beabout 0.05 mm to about 0.2 mm; from about 0.1 mm to about 0.3 mm; andfrom about 0.2 mm to about 0.6 mm. Control fluid and other fluids may beprovided to the apparatus through the use of a robotic device, or may beprovided manually.

A plurality of valves 161-170 control the flow of fluid into and out ofa microcantilever platform 180. In this embodiment, the valves 161-166are two-way valves that communicate with the fluid lines 141-148. Thevalves 161-166 all lead to a common line or manifold 800 comprisingfluid paths 801-803 and 445, 545, 645, and 745, and each valve has aninput and an output. For example, valve 166 has an input 121 forreceiving control fluid from control line 120 and an output 124 thatpermits fluid to flow both from fluid line 146 and fluid path 802. Inother words, valve 166 controls the output of fluid line 146 as well asthe output of fluid path 802, which runs under fluid line 146. As shownin FIG. 2, valves 167-170 are also two way valves and each of these hasa valve inlet 267-270 and a valve outlet 277-280. In order for fluid toflow though the housing, at least one of valves 167-170 must be open.

The valves 161-170 may be pneumatic valves that are activated by thecontrol fluid. In the embodiment of FIGS. 1-14, the control fluid, whenpressurized, serves to close the valves 161-170. In FIG. 1 the controlfluid has not been pressurized, thus the valves are all open, whereas inFIG. 3, the control fluid is pressurized and the valves 161-170 areclosed. When the control fluid is a high density gas, such as air, theresponse time of the valves quickens. The number valves in the apparatusmay be less than, more than or equal to the number of fluid lines.Similarly, the number of valves may be less than, equal to or more thanthe number of control lines.

The microcantilever platform 180 is disposed in the housing 150 andincludes a plurality of interaction cells 181-184. Each of theinteraction cells 181-184 has an inlet 171-174 for receiving one or morepreparation fluids and a sample fluid and an outlet, 271-274 as shown inFIG. 2, for releasing fluid from the cell through output lines 175-178.The interaction cells may be about 4 mm in diameter. For example, thediameter of the interaction cells may range from about 0.5 mm to about 6mm. In accordance with further embodiments of the invention, thediameter of the interaction cells may range from about 0.5 mm to about2.5 mm; from about 1 mm to about 3 mm; from about 2 mm to about 5 mm; orfrom about 3 mm to about 6 mm.

In accordance with an embodiment of the invention, the microcantileverplatform 180 is a micro-mechanical system wherein each of theinteraction cells includes at least one microcantilever configured todeflect in response to interactions with a chemical component of thesample fluid. Alternatively, each of the interaction cells 181-184 mayinclude a plurality of microcantilevers provided in a planar array offingers.

As used herein, the term “microcantilever” is a structural term thatrefers to a flexible beam that may be bar-shaped, V-shaped, or haveother shapes, depending on its application. One end of themicrocantilever may be fixed on a supporting base with another endstanding freely. Microcantilevers are usually of microscopic dimensions,for example, they can be about 50 μm to about 750 μm in length. Inaccordance with an embodiment of the invention, the microcantilevers arepreferably 200 nm to 700 μm in length, more preferably 250 μm to 600 μmin length, and most preferably 300 μm to 500 μm in length. Further, thewidth can be, for example, about 50 μm to about 300 μm. Eachmicrocantilever may be from about 0.5 μm to about 4.0 μm thick. Siliconand silicon nitride are the most common molecules used to fabricatemicrocantilevers. However, other molecules may be used for makingmicrocantilevers, including piezoelectric molecules, plastic moleculesand various metals.

In accordance with embodiments of the invention, the microcantileverscan be manufactured from ceramics, silicon, silicon nitride, othersilicon compounds, metal compounds, gallium arsenide, germanium,germanium dioxide, zinc oxide, diamond, quartz, palladium, tantalumpentoxide, and plastic polymers. Plastics can include: polystyrene,polyimide, epoxy, polynorbornene, polycyclobutene, polymethylmethacrylate, polycarbonate, polyvinylidene fluoride,polytetrafluoroethylene, polyphenylene ether, polyethyleneterephthalate, polyethylene naphthalate, polypyrrole, and polythiophene.Microcantilevers that are custom fabricated may be obtained from, forexample, Diffraction Ltd., Waitsfield, VT. Further, U.S. Pat. No.6,096,559 issued Aug. 1, 2000, and U.S. Pat. No. 6,050,722 issued Apr.18, 2000, describe fabrication of a microcantilever, including use ofmaterial such as ceramics, plastic polymers, quartz, silicon nitride,silicon, silicon oxide, aluminum oxide, tantalum pentoxide, germanium,germanium dioxide, gallium arsenide, zinc oxide, and silicon compounds.

Microcantilevers that can be employed in accordance with the inventionmay have a compotmd immobilized on the surface of a free end to detectand screen receptor/ligand interactions, antibody/antigen interactionsand nucleic acid interactions as is disclosed in U.S. Pat. No.5,992,226, issued on Nov. 30, 1999. Microcantilevers can be used todetect enzyme activities directed against a substrate located on asurface of the microcantilever. Deflection may be measured using eitherof optical or piezoelectric methods. Further, the microcantilevers ofthe embodiments of the invention can measure concentrations usingelectrical methods to detect phase difference signals that cari bematched with natural resonant frequencies as shown in U.S. Pat. No.6,041,642, issued Mar. 28, 2000. Determining a concentration of a targetspecies using a change in resonant properties of a microcantilever onwhich a known molecule is disposed, for example, a biomolecule selectedfrom DNA, RNA, and protein, is described in U.S. Pat. No. 5,763,768.

In accordance with embodiments of this invention, a method and apparatusfor detecting and measuring physical and chemical parameters in a samplemedia may use micromechanical potentiometric sensors as disclosed inU.S. Pat. No. 6,016,686, issued Jan. 25, 2000. Chemical detection of achemical analyte is described in U.S. Pat. No. 5,923,421, issued Jul.13, 1999. Further, magnetic and electrical monitoring of radioimmuneassays, using antibodies specific for target species which causemicrocantilever deflection (e.g., magnetic beads binding the target tothe microcantilever, as described in U.S. Pat. No. 5,807,758, issuedSep. 15, 1998) would be consistent with embodiments of the invention.

The term “first surface” as used herein refers to that geometric surfaceof a microcantilever designed to receive and bind to a ligand andfurther to an analyte. One or more coatings can be deposited upon thisfirst surface. The term “second surface” refers to the area of theopposite side of the microcantilever that is designed not to receive theligand or bind to the analyte. As the second surface is generally notcoated, it is generally comprised of the material from which themicrocantilever or microcantilever array is fabricated, prior to anycoating procedure applied to the first surface. Alternatively, it may becoated with a material different from the first surface's coating.

Coating of micromechanical sensors with various interactive molecules isdescribed in U.S. Pat. No. 6,118,124, issued Sep. 12, 2000. A coatingmaterial is deposited on a microcantilever by depositing a metal whichmay be selected from at least one of the group consisting of aluminum,copper, gold, chromium, titanium, silver, and mercury. Further, aplurality of metals may be deposited on a microcantilever by depositing,for example, a first layer of chromium and a second layer of gold, or afirst layer of titanium and a second layer of gold. Coatings may beamalgams or alloys comprising a plurality of metals.

In accordance with embodiments of the invention, a first surface of amicrocantilever can be fabricated to have an intermediate layer, forexample, sandwiched between the first surface comprising for example,gold, and the second surface, comprising for example silicon nitride.The intermediate layer may be an alloy comprising a plurality of metals.For example, the intermediate layer may be an amalgam comprising mercurywith at least one of chromium, silver, and titanium.

A microcantilever may deflect or bend from a first position to at leasta second position due to differential stress on a first surface of themicrocantilever in comparison to a second surface. That is amicrocantilever may deflect in response to the change in surface stressresulting from exposure of the microcantilever to a component of aparticular environment. A microcantilever may also deflect in responseto a change in the environment. A change in the environment may occur asthe result of adding a sample having or lacking an analyte, having ahigher or lower analyte concentration, adding or omitting a specificco-factor of an analyte, having a higher or lower concentration of theco-factor, having or lacking a specific inhibitor of an analyte, orhaving a higher or lower concentration of an inhibitor. Further, asample may be diluted or concentrated and a solution may experience achange in temperature, pH, conductivity or viscosity prior to, during orafter exposure to a microcantilever.

When one end of a microcantilever is fixed to a supporting base asdescribed above, deflection is measured by measuring a distance thedistal end of the microcantilever (i.e., the end distal to the end fixedto the supporting base) has moved. The distal end may move from a firstposition to a second position. In the first position, the biomaterial onthe first surface of the microcantilever has not yet bound to or reactedwith the analyte. In the second position, the biomaterial on themicrocantilever has bound to or has reacted with the analyte in theenvironment.

A “deflection characteristic”, as used herein, is a pattern ofdeflection of a microcantilever that is reproducible in extent ofdistance traveled, for example as measured in nm, and frequency per unittime. The deflection characteristic can distinguish specific conditionsof ligand and analyte, and further reaction conditions such astemperature, concentration, ionic strength, presence of cation or otherco-factors, preservatives, and other conditions well known to one of thechemical arts. The deflection under these conditions thereby can becomea signature for the specific reaction. A deflection characteristic iscalculated from a measurement of movement of the microcantilever uponaddition of a sample, or measurement of movement as a function ofconcentration of an analyte, a ligand, an inhibitor, or a co-factor. Adeflection characteristic may also be calculated as a function of pH, orof temperature, and the like.

Each of the interaction cells 181-184 may receive a different samplefluid as will be discussed in more detail below. A microprocessor can beincluded in an apparatus or a method, such that an integrated circuitcontaining the arithmetic, logic, and control circuitry required tointerpret and execute instructions from a computer program may beemployed to control activation of the the valves. Further,microprocessor components of the measuring devices may reside in anapparatus for detection of microcantilever deflection.

The apparatus may also include a plurality of expansion chambers 151-154for eliminating gas from fluids entering the interaction chamber181-184, and a waste line 190 with a waste outlet 191 for releasingwaste from the interaction cells 181-184 into a waste receptacle (item909 in FIG. 20). Further, each interaction cell 181-184 may be in fluidcommunication with its own waste receptacle or with a reservoir forcollecting the contents of the interaction cell in order to performfurther analysis on what is contained in the reservoir. Further analysismay include gel electrophoresis, and the gel electrophoresis may bemulti-dimensional. Additionally, at least one of the dimensions may bepolyacrylamide gel electrophoresis in the presence of a denaturingdetergent. Further analysis may also include mass spectroscopy.

The apparatus of FIGS. 1 and 2 may be a card or cartridge consisting ofabout 17 layers of one more plastic polymers. Such cards and cartridgesmay be custom manufactured, for example, by Micronics, Inc. of Redmond,Wash. These cards or cartridges may be mounted in a manifold thatreceives fluid pump lines or fluid from other fluid delivery devices.Similarly, the pumps may be part of the card as mentioned above. Theapparatus may also be mounted on a temperature-controlled platform. Theapparatus may be used to identify a particular molecule in one or moresample fluids, as is shown in FIGS. 3-14.

In FIG. 3, a control fluid, in this case a gas such as air, ispressurized in the control lines 111-120 through the inlets 101-110 toclose the valves 161-170. When all the valves have been closed, fluidcannot flow into or out of the interaction cells. Thus, all of thevalves are initially closed (by pressurizing a control fluid in thecontrol lines) and then opened (by de-pressurizing the control fluid) toallow liquid to flow into appropriate interaction cells. This is done sothat preparation fluids, such as linker, buffer, ligand solutions, andsample solutions containing an analyte may be input to the interactioncells 181-184 in a discriminatory manner. For example, a buffer solutionmay be input to all of the cells or to a subset of the cells, forexample, to three of the cells, two of the cells or only to one of thecells. Similarly, a different sample solution may be input to each ofthe cells, or to a subset of the cells.

FIG. 4 shows a linker solution being added to a first interaction cell.The term “linker solution” may include the following compounds:dithiobis(succinimidyl-undecanoate) (DSU), which can be purchased fromPierce Endogen, Inc. (Rockford, Ill.); long chainsuccinimido-6[3-(2-pyridyldithio)-propionamido] hexanoate (LCSPDP),which contains pyridyldithio and NHS ester reactive groups that reactwith sulfhydryl and amino groups and can be purchased from Pierce;succinimidyl-6[3-(2-pyridyldithio)-propionamido] hexanoate (SPDP), whichcontains pyridyldithio and NHS ester reactive groups that react withsulfflydryl and amino groups and can be purchased from Pierce; andm-maleimidobenzoyl-N-hydroxysuccinimide ester (MBS), which contains NHSester and maleimide reactive groups that react with amino and sulfhydrylgroups, and can be purchased from Pierce.

To add linker to the first interaction cell, inlets 109 and 106 do notreceive the control gas, thus no control gas is input to control lines119 and 116, and valves 165 and 170 are opened. The linker solutionflows from a fluid pump or other fluid delivery device to inlet 135 intofluid line 145. Since valve 165 is open, the fluid may then flow throughfluid path 445 into fluid path 446, and into expansion chamber 154. Gasmay optionally be eliminated from the linker solution in the expansionchamber 154, and the linker solution flows through fluid path 447 intointeraction cell 184 via inlet 174. Any outflow of fluid from theinteraction cell 184 will flow into output line 178, and because valve170 is open, the outflow will be stored in a waste receptacle (or in areservoir for collection) via fluid waste line 190 and waste outlet 191.

FIG. 5 illustrates how the linker solution may be added to the secondinteraction cell, while keeping all other interaction cells isolated, bypressurizing the control fluid in all control lines except control lines115 and 119, thus opening valves 165 and 169. As above, the linkersolution flows from a fluid pump to inlet 135 into fluid line 145 andthen through fluid paths 445 and 545. Note that the control lines 111,112, 117, and 118 intersect fluid lines 141, 142, 143 and 144respectively at a point above valves 161-164. Consequently, fluid mayflow from fluid path 445 to 545 in a relatively unrestricted manner. Atthis point the fluid will flow into fluid path 546, and then intoexpansion chamber 153. Gas is eliminated from the linker solution in theexpansion chamber 153, and the linker solution flows through fluid path547 into interaction cell 183 via inlet 173. Any outflow of fluid fromthe interaction cell 183 will flow into output line 177, and becausevalve 169 is open, the outflow will be stored in a waste receptacle viafluid waste line 190 and waste outlet 191.

FIGS. 6 and 7 show the linker solution being added to interaction cells182 and 181 respectively. In accordance with this embodiment, eachinteraction cell 182 and 181 will receive the linker solution while allother cells are isolated in the manner described above with respect toFIGS. 4 and 5. To add the linker solution to interaction cell 182,control fluid will not be pressurized in control lines 114 and 119,causing valves 165 and 168 to open. Linker solution will flow from afluid pump to inlet 135 into fluid line 145 and then through fluid paths445, 545, and 645. The fluid will then flow into fluid path 646, andinto expansion chamber 152. Gas will be eliminated from the linkersolution in the expansion chamber 152, and the linker solution will flowthrough fluid path 647 into interaction cell 182 via inlet 172. Outflowof fluid from the interaction cell 182 will flow into output line 176,and because valve 168 is open, the outflow will be stored in a wastereceptacle via fluid waste line 190 and waste outlet 191.

To add the linker solution to interaction cell 181, control fluid is notpressurized in control lines 113 and 119, causing valves 165 and 167 toopen. Linker solution will flow from a fluid pump to inlet 135 intofluid line 145 and then through fluid paths 445, 545, 645, and 745. Thefluid will then flow into fluid path 746, and into expansion chamber151. Gas will be eliminated from the linker solution in the expansionchamber 151, and the linker solution will flow through fluid path 747into interaction cell 181 via inlet 171. Outflow of fluid from theinteraction cell 181 will flow into output line 175, and because valve167 is open, the outflow will be stored in a waste receptacle via fluidwaste line 190 and waste outlet 191.

The linker solution may be added to a subset of the plurality ofinteraction cells, or to all of the interaction cells, illustrated herefor exemplary purposes only as four of the cells 181, 182, 183 and 184,by opening valve 165 with valves 167, 168, 169 and 170 simultaneously.Similarly, any subset of interaction cells may receive linker solutionsimultaneously by opening valve 165 and the valves that correspond tothe interaction cells to be filled. Further, waste line 190 may lead toa plurality of reservoirs, and the outflow from the interaction cellsmay be stored in respective reservoirs for further analysis. Valves maybe provided to insure that outflow from each interaction cell is storedin its corresponding reservoir. Alternatively, reservoir lines andoutlets may be provided for each interaction cell, rather than one lineand outlet (such as waste line 190 and outlet 191).

FIG. 8 is a graphical illustration of the embodiment of FIG. 1 showing awash solution added to a first interaction cell. The wash solution willflow from a fluid pump or other fluid delivery device to fluid line 148via inlet 138. In accordance with this embodiment, no control line is indirect communication with fluid line 148 (though such a control linecould be provided) thus, only control line 116 is de-pressurized. Valve170 is opened, allowing the wash solution to flow into fluid path 445via fluid paths 801-803. From this point, the wash process continues asdescribed above with respect to the linker solution and FIG. 4-7, toprovide each interaction cell with the wash solution.

FIG. 9 is a graphical illustration of the embodiment of FIG. 1 showing aligand solution, for example, an antibody solution, added to a firstinteraction cell. The ligand may react chemically with previouslyapplied linker molecules. The ligand solution flows from a fluid pump orother fluid delivery device to fluid line 146 via inlet 136. Controllines 116 and 110 are de-pressurized and valves 170 and 166 are opened,allowing the ligand solution to flow into fluid path 445 via fluid path803. From this point, the ligand solution proceeds through the apparatusas described above with respect to the linker and wash solutions toprovide each interaction cell with the ligand solution.

FIG. 10 is a graphical illustration of the embodiment of FIG. 1 showinga buffer solution added to a first interaction cell. The buffer solutionflows from a fluid pump or other fluid delivery device to fluid line 147via inlet 137. As was the case with the wash solution, no control lineis in direct communication with fluid line 147 (again, such a controlline could be provided), thus only control line 116 is de-pressurized.Valve 170 is opened, allowing the buffer solution to flow into fluidpath 445 via fluid paths 802-803. From this point, the buffer solutionproceeds to each interaction cell in accordance with the embodiments ofFIGS. 4-7. A wash process may follow the addition of the buffer solutionto each cell and will proceed as described above with respect to FIG. 8.

In FIG. 11, a first sample solution having an analyte, or a controlsolution, is added to the first interaction cell. The first samplesolution flows from a fluid pump or other fluid delivery device to fluidline 144 via inlet 134. Control lines 116 and 118 are de-pressurized andvalves 170 and 164 are opened, allowing the first sample solution toflow into fluid path 446 and into expansion chamber 154. From thispoint, the first sample solution proceeds to the interaction cell 184via fluid path 447 and inlet 174. Outflow of the first sample solutionfrom the interaction cell 184 will flow into output line 178, and theoutflow will be stored in a waste receptacle (or reservoir forcollection) via waste line 190 (or reservoir line) and waste outlet (orreservoir outlet) 191.

FIG. 12 is a graphical illustration showing that the second interactioncell may be provided with a second sample solution. To provideinteraction cell 183 with the second sample solution, control lines 115and 117 are de-pressurized, valves 169 and 163 are opened and the secondsample solution flows from a fluid pump to fluid line 143 via inlet 133.The second sample solution will flow into fluid path 546 and intoexpansion chamber 153. The second sample solution proceeds to theinteraction cell 183 via fluid path 547 and inlet 173. As above, outflowof the second sample solution from the interaction cell 183 will flowinto output line 177, and the outflow will be stored in a wastereceptacle (or reservoir for collection) via waste line 190 and wasteoutlet 191.

FIG. 13 illustrates a way to provide the third interaction cell 182 witha third sample solution, control lines 112 and 114 are de-pressurized,valves 162 and 166 are opened and the third sample solution flows from afluid pump to fluid line 142 via inlet 132. The third sample solutionwill flow into fluid path 646 and into expansion chamber 152 and gaswill be removed from the solution. The third sample solution proceeds tothe interaction cell 182 via fluid path 647 and inlet 172. Outflow ofthe third sample solution from the interaction cell 182 will flow intooutput line 176, and the outflow will be stored in a waste receptacle(or reservoir for collection) via waste line 190 and waste outlet 191.

FIG. 14 illustrates a way to provide the fourth interaction cell 181with a fourth sample solution. Here, control lines 111 and 113 arede-pressurized, valves 161 and 167 are opened and the fourth samplesolution flows from a fluid pump to fluid line 141 via inlet 131. Thefourth sample solution will flow into fluid path 746 and into expansionchamber 151, and gas will be removed from the solution. The third samplesolution proceeds to the interaction cell 181 via fluid path 747 andinlet 171. Outflow of the third sample solution from the interactioncell 181 will flow into output line 175, and the outflow will be storedin a waste receptacle (or reservoir for collection) via waste line 190and waste outlet 191.

Each of the interaction cells includes at least one microcantilever, oran array of microcantilevers, configured to deflect in response tochemical interactions with a component of the sample fluid. In aparticular embodiment of the invention, a planar array ofmicrocantilever fingers is disposed in each interaction cell such thatone or more microcantilever finger deflects with respect to the plane ofthe array in response to a reaction with a molecular component of thesample solution.

FIG. 15 is a graphical illustration showing an apparatus for performingmicrofluidic analysis in which the valves of the apparatus are normallyclosed in accordance with another embodiment of the invention. Unlikethe embodiment of FIG. 1, in FIG. 15, all of the valves 1051-1058 and1061-1064 are closed under normal atmospheric pressure (when only air isin the lines). This configuration reduces the duty cycle of theelectrical components of the system and minimizes the amount of currentneeded to drive the system. However, whether the valves are open orclosed under normal atmospheric conditions is purely arbitrary and eachof the embodiments of FIG. 1 and FIG. 15 may operate either way withrespect to the configuration of lines and valves. Additionally, inaccordance with the embodiment of FIG. 15, the fluid lines 1011-1019 andfluid inlets 1001-1008 are at the top of the figure, rather than at thebottom as in FIG. 1.

The apparatus includes a three-dimensional housing 1000 having aplurality of fluid lines 1011-1019. Each of the fluid lines 1011-1018has an inlet 1001-1008 for receiving a fluid from a fluid pump or otherfluid delivery apparatus. The housing 1000 also includes a plurality ofcontrol lines 1031-1042 in communication with the fluid lines 1011-1019.Each of the control lines 1031-1042 receives a control fluid from aninlet 1071-1082. The fluid lines 1011-1019, control lines 1031-1042 andfluid paths of this embodiment may be dimensioned in a manner similar tothe fluid lines, control lines, and fluid paths described with respectto FIG. 1. Here again, control fluid and other fluids may be provided tothe apparatus through the use of a robotic device, or may be providedmanually.

The plurality of valves 1051-1058 and 1061-1064 control the flow offluid into and out of a microcantilever platform 1020. The valves may betwo-way valves that function as three-way valves as described above withrespect to the embodiment of FIG. 1. Thus, each valve has an inlet andan outlet. For example, valve 1051 has a valve inlet 1082 for receivingthe control fluid from control line 1031, a valve outlet 1083 fortransmitting fluid from fluid line 1012 to the manifold 1100. The valves1051-1058 and 1061-1064 are activated (in this case opened) by thecontrol fluid. As above, when the control fluid is a high density gasthe response time of the valves quickens The valves may be activated ordeactivated under control of a computer program resident on amicroprocessor. Further, the number valves in the apparatus may be lessthan, more than or equal to the number of fluid lines. Similarly, thenumber of valves may be less than, equal to or more than the number ofcontrol lines.

The microcantilever platform 1020 is disposed in the housing 1000 andincludes a plurality of interaction cells 1021-1024. Each of theinteraction cells 1021-1024 has an inlet, such as 1025, for receivingone or more preparation fluids and a sample fluid and an outlet, such as1026, for releasing fluid from the cell through output lines 1095-1098.

The apparatus of FIG. 15 may further include a waste line 1200 with awaste outlet 1009 for releasing waste from the interaction cells1021-1024 into a waste receptacle. As was the case with the embodimentof FIG. 1, each interaction cell 1021-1024 may be in fluid communicationwith its own waste receptacle or with a reservoir for collecting thecontents of the interaction cell in order to perform further analysis onwhat is contained in the reservoir.

As was the case with the apparatus of FIG. 1, the embodiment of FIG. 15may be in the form of a card or cartridge comprising one more plasticpolymers. Preparation fluids, such as linker, buffer, ligand solutions,and sample solutions may be input to the interaction cells 1021-1024 ina discriminatory manner. A buffer solution may be input to all of thecells or to a subset of the cells, for example, to three of the cells,two of the cells or only to one of the cells. Similarly, a differentsample solution may be input to each of the cells, or to a subset of thecells.

FIG. 16 shows a solution being added to a first interaction cell. Toaccomplish this, inlets 1081 and 1079 receive the control gas, thuscontrol gas is input to control lines 1041 and 1039 respectively, andvalves 1057 and 1064 are opened. The solution flows from a fluid pump orother fluid delivery device to inlet 1008 into fluid line 1018. Sincevalve 1057 is open, the fluid may then flow through fluid path 1300 intofluid path 1400, and into interaction cell 1024 via inlet 1425. Anyoutflow of fluid from the interaction cell 1024 will flow into outputline 1098, and because valve 1064 is open, the outflow will be stored ina waste receptacle (or in a reservoir for collection) via fluid wasteline 1200 and waste outlet 1009.

The solution may be added to a subset of the plurality of interactioncells, or to all of the interaction cells, illustrated here forexemplary purposes only as four cells. Similarly, any subset ofinteraction cells may receive a solution simultaneously by opening thevalves that correspond to the appropriate interaction cells to be filled(as will be evident from the descriptions FIGS. 16-20). Further, thewaste line 1200 may lead to a plurality of reservoirs, and the outflowfrom the interaction cells may be stored in respective reservoirs forfurther analysis. Valves may be provided to insure that outflow fromeach interaction cell is stored in its corresponding reservoir.Alternatively, reservoir lines and outlets may be provided for eachinteraction cell, rather than one line and outlet.

FIG. 17 is a graphical illustration of the embodiment of FIG. 15 showinga solution added to a second interaction cell. Here, inlets 1080 and1078 receive the control gas, thus control gas is input to control lines1040 and 1038 respectively, and valves 1056 and 1063 are opened. Thesolution flows to inlet 1007 into fluid line 1017. Since valve 1056 isopen, the fluid may then flow through fluid path 1500 into fluid path1600, and into interaction cell 1023 via inlet 1525. Any outflow offluid from the interaction cell 1023 will flow into output line 1097,and because valve 1063 is open, the outflow will be stored in a wastereceptacle or reservoir via fluid waste line 1200 and waste outlet 1009.

FIG. 18 is a graphical illustration of the embodiment of FIG. 15 showinga solution added to a third interaction cell. Inlets 1075 and 1077receive the control gas, and control gas is input to control lines 1035and 1037 respectively. Valves 1055 and 1062 are opened. The solutionflows from a fluid pump or other fluid delivery device to inlet 1006into fluid line 1016. Since valve 1055 is open, the fluid may then flowthrough fluid path 1700 into fluid path 1800, and into interaction cell1022 via inlet 1725. Again, outflow of fluid from the interaction cell1022 will flow into output line 1096, and because valve 1062 is open,the outflow will be stored via fluid waste line 1200 and waste outlet1009.

FIG. 19 is a graphical illustration of the embodiment of FIG. 15 showinga solution added to a fourth interaction cell. Inlets 1074 and 1076receive the control gas, which is input to control lines 1034 and 1036respectively. Valves 1054 and 1061 are opened, and the solution flowsfrom to inlet 1005 into fluid line 1015. Since valve 1054 is open, thefluid may then flow through fluid path 1900 into fluid path 2000, andinto interaction cell 1021 via inlet 1225. Any outflow of fluid from theinteraction cell 1021 will flow into output line 1095, and because valve1061 is open, the outflow will be stored in a waste receptacle orreservoir via fluid waste line 1200 and waste outlet 1009.

FIG. 20 is a schematic flow chart illustrating fluidics system for usein accordance with a method for identifying an analyte in a plurality ofsample fluids in accordance with a further embodiment of the invention.In accordance with this embodiment, one or more preparation solutions901-904 are input into one or more of a plurality of interaction cells.At least one of the preparation fluids includes a ligand that hasaffinity for the analyte. Each interaction cell includes at least onemicrocantilever such that the ligand binds to the microcantilever. Atleast one sample solution 905-908 is input into one or more of theinteraction cells, and a deflection of the microcantilever in isdetected in each sample solution containing the analyte. In oneembodiment, the device may be mounted in a manifold and/or on atemperature-controlled platform. Outflow from the interaction cells910-913 may be stored in a waste receptacle 909 or in a reservoir forfurther analysis as described above.

One of the preparation fluids may be a solution of a linker 901 capableof covalently linking the ligand, here defined as the material affixedto a surface of the microcantilever, to the microcantilever. Anotherpreparation fluid may be a wash solution 902, and the wash solution maybe input to one or a plurality of the interaction cells one or moretimes. Yet another preparation fluid may be a ligand or a “receptor”solution 903, i.e., a biological macromolecule known to have affinityfor a specific binding portion, or a ligand for a class of analytes. Thereceptor can also be a ligand for an analyte, the presence and/or amountof which is to be detected in one or in a series of sample. Anotherpreparation fluid may be a buffer solution 904. The number of samplesolutions may equal the number of interaction cells or the number ofsample solutions may be less than the number of interaction cells.

The ligand may be a biomaterial, for example, a protein such as anenzyme or a synthetic polypeptide, or it can be a nucleic acid such asRNA or DNA. A biomaterial that is a macromolecule may comprise all or aportion of a nucleic acid or a protein. The protein or polypeptide maycomprise an epitope, an antibody, an antibody fragment, an enzyme, orany other embodiment of a molecule containing peptide bonds. The analyteto be detected or quantified in a sample may be a biomaterial such as amacromolecule, or an organic or inorganic small molecule. Similarly, theanalyte may be hormone, for example, the hormone may be a steroid forexample, a sex steroid or a glucocorticoid, or a polypeptide hormonesuch as a cytokine. Either of the ligand or the analyte may comprise allor a portion of an antibody or an antigenic material, or all or aportion of an enzyme.

Examples and methods for the use of the apparatus of the invention areshown in Table 1. In Example 1, the apparatuses of FIGS. 3-19 is used todemonstrate a movement or deflection of a plurality of microcantileversin a microcantilever array when a sample solution contains an analyte,such as a particular chemical or biological component, capable ofbinding to or inter acting with a ligand affixed to a surface of themicrocantilever. Cell A can be a reaction cell that provides a positivecontrol; deflection of microcantilevers is caused by interaction on asurface of the cantilever of components of fluids sequentially providedto cell A. Cell B can be a reference cell; for example, a control bufferknown to lack the analyte, is added to this cell instead of a sample.This control can determine the extent of microcantilever deflection thatoccurs as a result of interactions between preparation liquids such as alinker solution and an antibody solution, or other environmental forces.Cell C can be a negative control cell, for example, which has not beenexposed to linker solution. Microcantilever deflection in this cell candetermine the extent of ligand binding to a microcantilever surfacedirectly, in the absence of a cross-lining agent. Cell D can be anothercontrol cell, containing for example, bovine serum albumin instead ofthe biomaterial of interest, so that microcantilever deflection is ameasure of non-specific binding of the analyte.

The contents of all cited references are hereby incorporated byreference herein.

EXAMPLE 1

In accordance with step 1 of Example 1 as illustrated in Table 1, thecross-linking agent DSU (dithiobis(succinimidylundecanoate)) in a volumeof about 50 μl, is added to interaction cells A, B and D. DSU is a watersoluble bifunctional cross-linking agent.

In step 2, as herein exemplified, all of the cells receive a washsolution in a volume of about 300 μl per cell. In step 3, all of thecells can receive about 50 μl of an antibody solution (such as anantibody specific for an oncogene protein such as Brc A or Wilm's Tumor,WT-1). A buffer having a low pH is provided to interaction cells, forexample, to cells A, B and D, in a volume of about 50 μl per cell instep 4. This solution removes non-specifically bound material, i.e.,those molecules of material which have not reacted with thecross-linking agent. Cells are washed with about 300 μl of the washsolution in step 5. In step 6, a volume of a sample solution containing,for example, an unknown quantity of a material that can interact withthe antibody of step 3, for example, about 50 μl is provided to cells,for example, to cells A and C. A control material, e.g., bovine serumalbumin is provided to cell D in a volume of about 50 μl in step 7.Cells are washed, for example, with about 300 μl of the wash solution instep 8.

Further in Example 1, it should be noted that the wash steps can beperformed with the same solution, and that steps, for example, steps 6and 7, can be preformed simultaneously. Further, any of the wash stepsare optional in volume and timing; deflection of microcantilevers can beanalyzed throughout, although measurement of deflection following steps6 and 7 is most significant.

It is to be understood that a choice of a volume of fluid to use ismerely suggested here and can be varied from the suggested amounts.Volumes for other use in the methods and apparatuses herein can bestandardized within any given experiment according to a protocol to bedevised by a user of ordinary skill in the art, and such alternativevolumes are within the equivalents envisioned herein.

EXAMPLE 2

Example 2 is an illustration of how the apparatus described herein maybe used to identify a ligand in a plurality of sample solutions. Herecells A, B and C are reaction cells and cell D is used as a controlcell. A volume, for example, of about 50 μl of DSU is provided to eachcell in step 1. Next in step 2, a wash solution is provided to each cellin a volume of, for example, about 300 μl per cell. In steps 3 and 4,each cell is provided with about 50 μl of antibody solution and buffersolution respectively, and in step 5 the cells are subjected to anotherwash. A first sample solution, in a volume of about 50 μl, is then addedto cell A in step 6. A second sample solution, also in volume of about50 μl, is added to cell B in step 7, and a third sample solution of thesame volume is added to cell C in step 8. It should be noted that inaccordance with the apparatus described above, the first, second andthird sample solutions may be provided to cells A, B and C,respectively, in one step. All of the cells are subjected to an optionalwash process in step 9. Further, the solutions in one or more of thecells may be reused. That is, additional solutions may be added to oneor more of the cells for further analysis.

EXAMPLE 3

Example 3 illustrates how the apparatus described herein may be used todiagnose a patient simultaneously for one of a plurality of differentviruses. Cells A, B and C are reaction cells and cell D is used as acontrol cell. A volume, for example, of about 50 μl of DSU is providedto each cell in step 1. In step 2, a wash solution is provided to eachcell in a volume of, for example, about 300 μl per cell. In step 3 cellA is provided with about 50 μl of a first antibody solution. In step 4cell B is provided with about 50 μl of a second antibody solution, andin step 5 cell C is provided with about 50 μl of a third antibodysolution. Each antibody solution can have binding determinants directedagainst one of the viruses for the diagnosis. A volume of about 50 μl,of buffer solution is added to each of the cells step 6. All of thecells are then provided with about 300 μl of a wash solution in step 7,and in step 8 a volume of about 50 μl of a first, second, third samplesolutions is provided to cells A, B, and C. The first, second and thirdantibody solutions may be provided to cells A, B and C, respectively, inone step. All of the cells can be subjected to an optional wash processin step 9.

Although various exemplary embodiments of the invention have beendisclosed, it should be apparent to those skilled in the art thatvarious changes and modifications can be made which will achieve some ofthe advantages of the invention without departing from the true scope ofthe invention. TABLE I Example 1 Total Vol μl A B C D Step Solution (AllCells) Reaction Ref NSB BSA 1 DSU 50 + + 0 + 2 Wash 300 + + + + 3 Ab50 + + + + 4 Hbuffer 50 + + 0 + 5 Wash 300 + + + + 6 Sample 50 + 0 + 0 7BSA 50 0 0 0 + 8 Wash 300 + + + + Total Vol μl A B C D Step Solution(All Cells) Reaction Reaction Reaction Control Example 2 1 DSU50 + + + + 2 Wash 300 + + + + 3 Ab 50 + + + + 4 Hbuffer 50 + + + + 5Wash 300 + + + + 6 Sample 1 50 + 0 0 0 7 Sample 2 50 0 + 0 0 8 Sample 350 0 0 + 0 9 Wash 300 + + + + Example 3 1 DSU 50 + + + + 2 Wash300 + + + + 3 Ab 1 50 + 0 0 0 4 Ab 2 50 0 + 0 0 5 Ab 3 50 0 0 + 0 6Hbuffer 50 + + + + 7 Wash 300 + + + + 8 Sample 50 + + + 0 9 Wash300 + + + +

1-27. (canceled)
 28. A method for identifying an analyte in a pluralityof sample fluids, the method comprising: causing a preparation solutionto flow into one or more of a plurality of interaction cells, each ofthe interaction cells including a plurality of microcantilevers, thepreparation solution including a ligand that binds to themicrocantilever and has affinity for the analyte; causing at least onesample fluid to flow into the one or more interaction cells; anddetecting a deflection of the microcantilevers in each sample fluidcontaining the analyte.
 29. A method according to claim 28, whereincausing a preparation solution to flow into one or more of the pluralityof interaction cells includes causing a linker solution to flow into oneor more of the interaction cells, the linker capable of binding theligand to the microcantilevers.
 30. A method according to claim 28,wherein causing a preparation solution to flow into one or more of theplurality of interaction cells includes causing a wash solution to flowinto one or more of the interaction cells.
 31. A method according toclaim 28, wherein causing a preparation solution to flow into one ormore of the plurality of interaction cells includes causing a receptorsolution to flow into one or more of the interaction cells.
 32. A methodaccording to claim 28, wherein causing a preparation solution to flowinto one or more of the plurality of interaction cells includes causinga buffer solution to flow into one or more of the interaction cells. 33.A method according to claim 28, wherein the number of sample fluidsequals the number of interaction cells.
 34. A method according to claim28, wherein the number of sample fluids is less than the number ofinteraction cells.
 35. A method according to claim 28, wherein theligand is selected from a group consisting of a protein and a nucleicacid.
 36. A method according to claim 35, wherein the nucleic acid isRNA.
 37. A method according to claim 35, wherein the nucleic acid isDNA.
 38. A method according to claim 35, wherein the protein is anepitope.
 39. A method according to claim 35, wherein the protein is anenzyme.
 40. A method according to claim 35, wherein the protein is apolypeptide.
 41. A method according to claim 28, wherein the analyte isselected from a group consisting of all or a portion of a nucleic acidand a protein.
 42. A method according to claim 28, wherein the analyteis a hormone.
 43. A method according to claim 42, wherein the hormone isselected from a group consisting of a steroid and a polypeptide.
 44. Amethod according to claim 28, wherein each of the ligand and the analyteis selected from a group consisting of an antibody and an antigen.
 45. Amethod according to claim 28, further comprising mounting theinteraction cells on a temperature-controlled platform. 46-47.(canceled)
 48. A method according to claim 28, wherein the plurality ofinteraction cells is four interaction cells.
 49. A method foridentifying a presence of an analyte in each of a plurality of samplefluids, the method comprising: providing one or more of a plurality ofinteraction cells, wherein each of the interaction cells including aplurality of microcantilevers, wherein the microcantilevers within eachinteraction cell are identically configured to include a ligand bound tothe microcantilever, wherein the ligand has affinity for the analyte;causing at least one sample fluid to flow into at least one interactioncell; and detecting the presence of the analyte in the sample fluid bydetecting a deflection of the microcantilevers in the interaction cellcontaining the sample containing the analyte.
 50. A method according toclaim 49, wherein the interaction cells are within a housing.
 51. Amethod according to claim 49, wherein the plurality of interaction cellsis at least four interaction cells.
 52. A method according to claim 51,wherein the plurality of microcantilevers in each interaction cell is atleast four.
 53. A method according to claim 49, further comprising priorto detecting the presence of the analyte, mounting the interaction cellson a temperature-controlled platform.
 54. A method according to claim49, wherein the ligand is selected a group consisting of a protein and anucleic acid.
 55. A method according to claim 49, wherein the analyte isselected from a group consisting of a hormone, an enzyme, an antibodyand an antigen.
 56. A method according to claim 49, wherein causing atleast one sample solution to flow into the interaction cell is receivingfluid from a fluid delivery device.
 57. A method according to claim 56,wherein the fluid delivery device comprises fluid pump lines.
 58. Amethod for identifying a presence of an analyte in sample fluids, themethod comprising: providing a cartridge comprising a housing havingfour interaction cells and fluid pump lines connecting a fluid deliverydevice to each of the interaction cells, the housing configured formounting on a temperature-controlled platform, and wherein each of theinteraction cells including a plurality of microcantilevers, wherein themicrocantilevers within each interaction cell are identically configuredto include a ligand bound to the microcantilever, the ligand havingaffinity for the analyte; causing at least one sample fluid to flow intoat least one interaction cell; and detecting the presence of the analytein the sample fluid by detecting a deflection of the microcantilevers inthe interaction cell containing the sample containing the analyte.